ABSTRACT In this revised application, we propose a new pre- and post-doctoral training program at the University of Florida: Breathing REsearch And THErapeutics (BREATHE). Our proposal is to create a training program focused on the respiratory neuromuscular system, emphasizing the discovery of new knowledge and its translation to neuromuscular disorders that compromise breathing and airway defense. Diminished breathing capacity, unstable breathing and/or aspiration pneumonia from inadequate airway defense are hallmarks of many neuromuscular disorders, and respiratory failure is the most common cause of death. However, despite the fundamental importance of breathing and airway defense to the quality and duration of life in patients with degenerative neuromuscular diseases (eg. Muscular Dystrophy, Pompe Disease, ALS) or neural injury (eg. spinal cord injury), we know of no other training program with similar focus on breathing and airway defense in in these conditions. Our proposal directly addresses this critical gap in NHLBI funded research training. The ultimate goal of the BREATHE Training Program is to develop a unique cohort of researchers with strong foundations in basic research on respiratory neuromuscular biology, and a strong appreciation for the needs/realities of translational research in our attempts to develop treatments for impaired breathing and/or airway defense. Our perspective is that we can accelerate progress towards development of effective treatments for impaired breathing capacity/stability in diverse neuromuscular disorders by training investigators with: 1) a well-developed and comprehensive conceptual framework embracing similarities and differences between neuromuscular clinical disorders; and 2) a state-of-the-art ?tool kit,? providing the technological know- how to perform meaningful investigations in animal models and humans with spontaneous disease. We will train individuals with diverse academic backgrounds, including neuroscience, muscle biology, engineering and/or clinical training (physicians, physical or speech therapists and veterinarians; including multiple specialties in each group). A hallmark of our program will be ?cross-training,? where basic scientists are exposed to meaningful clinical experiences, and clinician scientists establish strong basic research foundations. We will capitalize on existing, and building strengths at the University of Florida to provide an integrated research-training program in respiratory neuromuscular biology and translational research. The UF Health Science Center has demonstrated its commitment to this area of research by creating a new Center for Respiratory Research and Rehabilitation. This Center, and other strengths at the UF Health Science Center, will provide an exceptional academic environment for the BREATHE Training Program.